nmda
Table of Contents
N-methyl-D-aspartate (NMDA) and NMDA receptors (NMDAR)
Introduction
- NMDA is an amino acid derivative that acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor
- unlike glutamate, NMDA only binds to and regulates the NMDA receptor and has no effect on other glutamate receptors (such as those for AMPA and kainate)
- NMDA receptors are thought to mediate alcohol withdrawal symptoms such as agitation and perhaps seizure
- at homeostatic levels NMDA plays an essential role as a neurotransmitter and neuroendocrine regulator
N-methyl-D-aspartate receptors (NMDAR)
- agonist binding to its NR2 subunits results in a non-specific cation channel opening, which can allow the passage of Ca2+ and Na+ into the cell and K+ out of the cell
- will only open if glutamate is in the synapse and concurrently the postsynaptic membrane is already depolarized - acting as coincidence detectors at the neuronal level
- the excitatory postsynaptic potential (EPSP) produced by activation of an NMDA receptor also increases the concentration of Ca2+ in the cell.
GluN2B-containing NMDARs
- this receptor is critical for promoting physiological synaptic plasticity and neuronal viability.1)
NMDAR antagonists
-
- amantadine
- dextromethorphan (DXM)
Anti-NMDA receptor encephalitis
- an autoimmune condition, with the primary target of antibodies being the GluN1 subunit of the N-methyl-D-aspartate receptors (NMDAR) in the brain
- rare: one in 1.5 million people per year but is is relatively common compared to other paraneoplastic disorders.
- 80% are female
- can occur at any age but most commonly under age 45yrs
- 1st described in 2007
- aetiology
- tumours
- half of cases are associated with tumors, most commonly teratomas of the ovaries
- Herpes simplex virus (HSV) encephalitis
- accounts for ~half the cases in children
- other causes
- clinical features
- fever, headache, malaise, flu-like illness initially which may precede onset of encephalitis features by days or weeks
- often followed by delusions and hallucinations with agitation and confusion
- may then develop seizures or motor disturbances (“piano playing”, “pedalling”), and some develop catatonia
- 4% mortality rate
- 10% recurrence rate
- Dx
- NMDA receptor antibodies can be detected in serum and/or CSF
- Rx
- remove cause if possible
- immunosuppression
nmda.txt · Last modified: 2025/02/16 22:45 by gary1